Rise In Systemic Vascular Resistance Research Articles

Hyperoxygenation in pregnancy exerts a more profound effect on cardiovascular hemodynamics than is observed in the nonpregnant state

Supplemental oxygen is administered to pregnant women in many different clinical scenarios in obstetric practice. Despite the accepted uses for maternal hyperoxygenation, the impact of hyperoxia on maternal hemodynamic indices has not been evaluated. As a result, there is a paucity of data in the literature in relation to the physiological changes to the maternal circulation in response to supplemental oxygen. The hemodynamic effects of oxygen therapy are under-recognized and the impact of hyperoxygenation on maternal hemodynamics is currently unknown. Using noninvasive cardiac output monitoring which employs transthoracic bioreactance, we examined the effect of brief hyperoxygenation on cardiac index, systemic vascular resistance, blood pressure, stroke volume, and heart rate in pregnant mothers during the third trimester, compared with those effects observed in a nonpregnant population subjected to the same period of hyperoxygenation. Hemodynamic monitoring was performed in a continuous manner over a 30-minute period using noninvasive cardiac output monitoring. Hyperoxygenation (O2 100% v/v inhalational gas) was carried out at a rate of 12 L/min via a partial non-rebreather mask for 10-minutes. Cardiac index, systemic vascular resistance, stroke volume, heart rate, and blood pressure were recorded before hyperoxygenation, at completion of hyperoxygenation, and 10 minutes after the cessation of hyperoxygenation. Two-way analysis of variance with repeated measures was used to assess the change in hemodynamic indices over time and the differences between the 2 groups. Forty-six pregnant and 20 nonpregnant women with a median age of 33 years (interquartile range, 26-38 years) and 32 years (interquartile range, 28-37 years) were recruited prospectively, respectively (P=.82). The median gestational age was 35 weeks (33-37 weeks). In the pregnant group, there was a fall in cardiac index during the hyperoxygenation exposure period (P=.009) coupled with a rise in systemic vascular resistance with no recovery at 10 minutes after cessation of hyperoxygenation (P=.02). Heart rate decreased after hyperoxygenation exposure and returned to baseline by 10 minutes after cessation of therapy. There was a decrease in stroke volume over the exposure period, with no change in systolic or diastolic blood pressure. In the nonpregnant group, there was no significant change in the cardiac index, systemic vascular resistance, stroke volume, heart rate, or systolic or diastolic blood pressure during the course of exposure to hyperoxygenation. Hyperoxygenation during the third trimester is associated with a fall in maternal cardiac index and a rise in systemic vascular resistance without recovery to baseline levels at 10 minutes after cessation of hyperoxygenation. The hemodynamic changes that were observed in this study in response to hyperoxygenation therapy during pregnancy could counteract any intended increase in oxygen delivery. The observed maternal effects of hyperoxygenation call for a reevaluation of the role of hyperoxygenation treatment in the nonhypoxemic pregnant patient.

The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia.

Pre-eclampsia (PE) is the most frequently encountered medical complication during pregnancy. It is characterized by a rise in systemic vascular resistance with a relatively low cardiac output and hypovolemia, combined with severe proteinuria. Despite the hypovolemia, renin-angiotensin system (RAS) activity is suppressed and aldosterone levels are decreased to the same degree as renin. This suggests that the RAS is not the cause of the hypertension in PE, but rather that its suppression is the consequence of the rise in blood pressure. Abnormal placentation early in pregnancy is widely assumed to be an important initial event in the onset of PE. Eventually, this results in the release of anti-angiogenic factors [in particular, soluble Fms-like tyrosine kinase-1 (sFlt-1)] and cytokines, leading to generalized vascular dysfunction. Elevated sFlt-1 levels bind and inactivate vascular endothelial growth factor (VEGF). Of interest, VEGF inhibition with drugs like sunitinib, applied in cancer patients, results in a PE-like syndrome, characterized by hypertension, proteinuria and renal toxicity. Both in cancer patients treated with sunitinib and in pregnant women with PE, significant rises in endothelin-1 occur. Multiple regression analysis revealed that endothelin-1 is an independent determinant of the hypertension and proteinuria in PE, and additionally a renin suppressor. Moreover, studies in animal models representative of PE, have shown that endothelin receptor blockers prevent the development of this disease. Similarly, endothelin receptor blockers are protective during sunitinib treatment. Taken together, activation of the endothelin system emerges as an important pathway causing the clinical manifestations of PE. This paper critically addresses this concept, taking into consideration both clinical and preclinical data, and simultaneously discusses the therapeutic consequences of this observation.

A Review of Systemic Vasodilators in Low Cardiac Output Syndrome Following Pediatric Cardiac Surgery.

Following surgery for congenital heart disease, patients develop a predictable and progressive decline in cardiac output known as low cardiac output syndrome. During low cardiac output states, a compensatory response to increase systemic perfusion occurs both innately and as part of the postoperative pharmacologic support strategies intended to increase or sustain adequate oxygen delivery. The result typically involves a rise in systemic vascular resistance and heart rate. These and other responses may actually limit the ability of the recently operated heart to provide sufficient cardiac output to meet the oxygen demands of the body. In order to improve systemic oxygen delivery, clinicians have increasingly employed systemic vasodilator therapy to reduce afterload and improve ventriculoarterial coupling. This review will summarize currently utilized pharmacologic agents that promote systemic vasodilation and improve cardiac output through afterload reduction. This article addresses the fourth of eight topics comprising the special issue entitled "Pharmacologic strategies with afterload reduction in low cardiac output syndrome after pediatric cardiac surgery".

Acute perioperative hemodilution without using hydroxyethyl starch : hemodynamic alterations under "controlled" hypovolemia

Up to now hydroxyethyl starch preparations have frequently been used to compensate for volume deficits accompanying blood withdrawal during acute normovolemic hemodilution. This approach was questioned with respect to the current limitations for use of hydroxyethyl starch solutions imposed by the European Medicines Agency. Because crystalloids distribute evenly across the whole extracellular compartment, 80 % of the infused solution will be "lost" to the interstitial space. Thus, a physiological adjustment of blood loss caused by hemodilution with crystalloids alone (1:5 ratio) seems hardly feasible and according to current data perhaps not even desirable. A 3:1 ratio (crystalloids versus blood loss) as applied in the current study can be regarded as a practical compromise between physiological needs and recommendations according to the literature (1.4:1) but will lead to moderate hypovolemia the hemodynamic consequences of which are not well described. The current study investigates the hemodynamic impact of a hemodilution with crystalloids under the precondition of a 3:1 substitution ratio compared to withdrawn blood. In the context of acute perioperative hemodilution 10 otherwise healthy women graded I and II on the American Society of Anesthesiologists (ASA) classification scheduled for open gynecological cancer surgery underwent an average blood withdrawal of 1097 ± 285ml which was substituted by an average of 3430 ± 806ml of Ringer's lactate. The resulting deficit in blood volume was exactly quantified by a double tracer technique. Hemodynamic changes were evaluated by a combination of thermodilution and pulse contour analysis (PiCCO system®). Subsequently, the remaining volume deficit was compensated by 245 ± 64ml of a 20 % albumin solution and hemodynamic parameters were again evaluated. When infusing Ringer's lactate in a 3:1 ratio compared to the actual blood loss, the blood volume decreased by 12 %. The volume effect of Ringer's lactate proved to be 17 %. While mean arterial pressure and heart rate remained constant, key hemodynamic parameters changed relevantly during the time course. A significant rise in cardiac output and myocardial contractility could be observed which was accompanied by a decrease in systemic vascular resistance. In contrast, cardiac preload and the parameters representing pulmonary vascular permeability remained unaltered. The infusion of 245 ± 64ml of a 20 % albumin solution nearly completely restituted blood volume and led to an insignificant rise in systemic vascular resistance but did not normalize cardiac output or myocardial contractility. In the study population, the loss of intravascular fluid during perioperative haemodilution could be compensated by an increase in cardiac performance. However, whether patients with a reduced cardiac capacity (i.e. older patients) are capable to improve their cardiac output sufficiently in order to compensate hypovolemia accompanying perioperative haemodilution with crystalloids remains questionable.

Anesthetic management of aortocaval fistula repair associated with aortic valve replacement, severe aortic regurgitation, and bacterial endocarditis

We report a case of an adult male who had received a gunshot to the abdomen 12years earlier. He presented with manifestations of high-output congestive heart failure (CHF), aortic regurgitation (AR), and pulmonary septic embolism. Further investigation revealed an aortocaval fistula (ACF). Following endovascular repair of the ACF, we observed an immediate rise in systemic vascular resistance (SVR), decrease in central venous pressure (CVP), increase in regurgitant flow across the aortic valve, and decrease in central mixed venous oxygenation. A combination of vasodilators and vasopressors was used to maintain hemodynamics. Milrinone infusion was necessary after cardiopulmonary bypass to maintain cardiac output. Even though local anesthesia and light sedation were used for ACF closure, the hemodynamics changed dramatically throughout the procedure. ACF closure under local anesthesia and sedation is preferred because the hemodynamics alterations under local anesthesia are less severe. The rise in SVR and regurgitant flow across aortic valve is less dramatic. As a result, hemodynamic management and separation from cardiopulmonary bypass are easier.

Preoperative ephedrine counters hypotension with propofol anesthesia during valve surgery: A dose dependent study

The prophylactic use of small doses of ephedrine may counter the hypotension response to propofol anesthesia with minimal hemodynamic changes. One hundred-fifty patients scheduled for valve surgery were randomly assigned into five groups (n = 30 for each) to receive saline, 0.07, 0.1, or 0.15 mg/kg of ephedrine, or phenylephrine 1.5 μg/kg before induction of propofol-fentanyl anesthesia. After induction, patient receiving ephedrine had higher mean arterial pressure, systemic vascular resistance (SVRI), cardiac (CI), stroke volume (SVI), and left ventricular stroke work (LVSWI) indices. Patients received 0.15 mg/kg of ephedrine showed additional increased heart rate and frequent ischemic episodes (P < 0.001). However, those who received phenylephrine showed greater rise in SVRI, reduced CI, SVI, and LVSWI and more frequent ischemic episodes. We conclude that the prophylactic use of small doses of ephedrine (0.07-0.1 mg/kg) is safe and effective in the counteracting propofol-induced hypotension during anesthesia for valve surgery.

Tilt training increases the vasoconstrictor reserve in patients with neurally mediated syncope evoked by head-up tilt testing

Tilt training is a useful therapeutic option in neurally mediated syncope (NMS). We tested the hypothesis that tilt training will restore orthostatic tolerance by increasing the degree of vasomotor reserve during sustained orthostatic stress. METHODS AND RESULTS In this follow-up study we enrolled 17 patients (age 31 +/- 22 years, 11 females) with a clinical diagnosis of NMS and two consecutive positive tilt tests. The head-up tilt test was repeated day after day: one session per day. All patients were instructed to continue a programme of daily standing training at home. Follow-up tilt testing was performed after a period of 6 weeks in 14 patients. ECG and finger arterial blood pressure (Portapres) were recorded during subsequent tilt testing. Left ventricular stroke volume (SV), cardiac output, and systemic vascular resistance were computed from the pressure pulsations (Modelflow). Spontaneous cardiac baroreflex sensitivity was estimated by cross-spectral analysis of heart rate (HR) and systolic blood pressure. In all patients, orthostatic tolerance was restored after 4.1 +/- 0.9 tilt sessions, median 4. The follow-up tilt test was also negative in all patients. This was accompanied by a significant rise in systemic vascular resistance to compensate for a postural reduction in SV in the sustained head-up tilt position. No evidence could be provided of altered baroreflex control of HR after tilt training. Tilt training restores orthostatic tolerance at least in part by increasing the amount of vasoconstriction that can ultimately be made available during sustained orthostatic stress. The increased vasoconstrictor reserve is preserved after 6 weeks of continued standing training at home.

Mechanisms of Disease: the tissue kallikrein–kinin system in hypertension and vascular remodeling

The pathogenesis of arterial hypertension often involves a rise in systemic vascular resistance (vasoconstriction and vascular remodeling) and impairment of salt excretion in the kidney (inappropriate salt retention despite elevated blood pressure). Experimental and clinical evidence implicate an imbalance between endogenous vasoconstrictor and vasodilator systems in the development and maintenance of hypertension. Kinins (bradykinin and lys-bradykinin) are endogenous vasodilators and natriuretic peptides known best for their ability to antagonize angiotensin-induced vasoconstriction and sodium retention. In humans, angiotensin-converting enzyme inhibitors, a potent class of antihypertensive agents, lower blood pressure at least partially by favoring enhanced kinin accumulation in plasma and target tissues. The beneficial actions of kinins in renal and cardiovascular disease are largely mediated by nitric oxide and prostaglandins, and extend beyond their recognized role in lowering blood pressure to include cardioprotection and nephroprotection. This article is a review of exciting, recently generated genetic, biochemical and clinical data from studies that have examined the importance of the tissue kallikrein-kinin system in protection from hypertension, vascular remodeling and renal fibrosis. Development of novel therapeutic approaches to bolster kinin activity in the vascular wall and in specific compartments in the kidney might be a highly effective strategy for the treatment of hypertension and its complications, including cardiac hypertrophy and renal failure.

Regulation of oxygen delivery during induced polycythemia in exercising dogs

Previous studies have concluded that polycythemia decreases oxygen delivery primarily because of a large fall in cardiac output associated with a rise in systemic vascular resistance that has been attributed to increased blood viscosity. However, because other studies have shown that polycythemia may not reduce oxygen delivery, an alternative hypothesis is that cardiac output falls in response to a rising oxygen content, thereby maintaining oxygen delivery constant. To determine whether oxygen content participates in the regulation of cardiac output during polycythemia, we studied eight chronically instrumented dogs trained to exercise on a treadmill. The dogs underwent exchange transfusion with packed red blood cells containing methemoglobin, which caused an increase in hematocrit from 35 +/- 1 to 50 +/- 1% and in viscosity, with little change in oxygen content. The expected fall in exercise cardiac output failed to occur after exchange transfusion with red blood cells containing methemoglobin (7.5 +/- 4 vs. 6.8 +/- 0.5 l/min; P = not significant), and there was no rise in systemic vascular resistance. Methylene blue was then administered intravenously to facilitate conversion of methemoglobin to oxyhemoglobin, which increased oxygen content (12.8 +/- 0.9 vs. 18.4 +/- 0.9 vol%; P < 0.01) with no change in hematocrit or viscosity. Resting cardiac output did not change significantly, but there was a significant decrease in exercise output (6.8 +/- 0.5 vs. 5.8 +/- 0.4 l/min; P < 0.05). Thus we conclude that the fall in cardiac output seen in acute polycythemia results in part from the regulation of oxygen delivery and is not due solely to increased blood viscosity.

Acute aortic rupture in a dog with spirocercosis following the administration of medetomidine : clinical communication

Spirocercosis is an emerging disease in veterinary medicine. A strong suspicion of spirocercosis is usually evident after a thorough clinical examination and radiography of the chest has been performed. Lesions seen on radiography include an oesophageal mass, spondylitis and oesophageal air. Unfortunately, radiography is not diagnostic and additional diagnostic procedures are required to confirm the diagnosis. Endoscopy is commonly performed to diagnose the condition. The dog presented in this study had radiographic and clinical signs consistent with spirocercosis and definitive diagnosis was required. Shortly after sedation with medetomidine, the dog went into cardiac arrest and failed to respond to resuscitative measures. On post mortem, the diagnosis of spirocercosis was confirmed and the cause of death was identified as acute aortic rupture. Aortic aneurysms are not an uncommon finding and cause of acute death in dogs with spirocercosis. The acute rupture of the aorta in this case is most probably the result of cardiovascular changes associated with the administration of medetomidine. Medetomidine causes an acute rise in systemic vascular resistance with hypertension. The increase in shear stress across the weakened aortic wall resulted in rupture. Caution with the use of medetomidine in patients with spirocercosis is advised.

Cardiorespiratory adjustments during hypercarbia in rainbow trout Oncorhynchus mykiss are initiated by external CO(2) receptors on the first gill arch.

Experiments were performed to test the hypothesis that the marked ventilatory and cardiovascular responses to hypercarbia in rainbow trout Oncorhynchus mykiss arise from specific stimulation of chemoreceptors localised to the first gill arch. This was accomplished by measuring cardiorespiratory variables during acute hypercarbia (20 min at P(CO(2))=8 mmHg; 1 mmHg=0.133 kPa) in fish subjected to selective bilateral extirpation of the first gill arch. The cardiovascular responses to hypercarbia in the intact fish included a significant bradycardia (from 75.0+/-1.6 to 69.0+/-2.0 beats min(-1); means +/- S.E.M.; N=16), an increase in dorsal aortic blood pressure (from 30.8+/-1.5 to 41.9+/-2.5 mmHg; N=16) and a rise in systemic vascular resistance (from 1.1+/-0.1 to 1.4+/-0.1 mmHg ml(-1) kg(-1) min(-1); N=16). Removal of the first gill arch or pre-treatment with the muscarinic receptor antagonist atropine prevented the hypercarbic bradycardia without affecting the pressure or resistance responses. Correlation analysis, however, revealed shallow but significant inverse relationships between water P(CO(2)) and cardiac frequency in both atropinised (r(2)=0.75) and gill-extirpated (r(2)=0.90) fish, suggesting a direct mild effect of CO(2) on cardiac function. The ventilatory response to hypercarbia in the intact fish consisted of an increase in ventilation amplitude (from 0.62+/-0.06 to 1.0+/-0.13 cm; N=16) with no change in breathing frequency. Removal of the first gill arch lowered resting breathing frequency and prevented the statistically significant elevation of breathing amplitude. Gill extirpation, however, did not totally abolish the positive correlation between water P(CO(2)) and ventilation amplitude (r(2)=0.84), suggesting the presence of additional (although less important) chemoreceptive sites that are not confined to the first gill arch. Plasma catecholamine levels were elevated during hypercarbia, and this response was unaffected by prior gill extirpation. To assess whether the CO(2) chemoreceptors of the first gill arch were sensing water and/or blood P(CO(2)), bolus injections of CO(2)-enriched water or saline were made into the buccal cavity or caudal vein, respectively. Injections of CO(2)-enriched water to preferentially stimulate external receptors evoked catecholamine release and cardiorespiratory responses that closely resembled the responses to hypercarbia. As in hypercarbia, extirpation of the first gill arch prevented the bradycardia and the increase in ventilation amplitude associated with externally injected CO(2)-enriched water. Except for a slight decrease in cardiac frequency (from 73.0+/-2.8 to 70.3+/-3.5 beats min(-1); N=11), injection of CO(2)-enriched saline to preferentially stimulate internal chemoreceptors did not affect any measured variable. Taken together, these data indicate that, in rainbow trout, the bradycardia and hyperventilation associated with hypercarbia are triggered largely by external CO(2) chemoreceptors confined to the first gill arch.

The acute increases in vasomotor tone and blood pressure induced by carotid artery occlusion are modulated by platelet-activating factor (PAF) independently of nitric oxide release

The purpose of the present study was to investigate the involvement of nitric oxide (NO) in the modulatory role of platelet-activating factor (PAF, 1- O-hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine), a vasoactive phospholipid mediator synthesized by endothelial cells, on the vascular tone and arterial blood pressure. In pentobarbitone-anaesthetized rabbits, unloading of the carotid sinus baroreceptors by a bilateral carotid artery occlusion elicited a reflex rise in systemic vascular resistance, which was markedly potentiated by pretreating the animals with the PAF receptor antagonist WEB 2086 ([3-4-(2-chlorphenyl-)-9-methyl-6H-thieno-3,2-f-1,2,4-triazolo-4,3- α-1,4-diazepin-2-yl-(4-morpholinyl)-l-propanone]; 5 mg/kg, i.v.). In contrast, the inhibition of the biosynthesis of NO via NO synthase using N ω-nitro- l-arginine methyl ester ( l-NAME) neither affected the systemic vasoconstriction induced by carotid artery occlusion nor modified the potentiating effect of WEB 2086. The haemodynamic alterations induced by l-NAME administration were corrected by continuous infusions of the directly-acting vasodilators sodium nitroprusside or diazoxide. The results of the present study confirm previous studies from our group suggesting the involvement of PAF in a negative feedback mechanism effective in the local regulation of vasomotor tone in anaesthetized rabbits, but exclude the participation of NO in this process.

Total intravenous anaesthesia using propofol, gamma-hydroxybutyrate or midazolam in combination with sufentanil for patients undergoing coronary artery bypass surgery

Total intravenous anaesthesia (TIVA) using propofol, gamma-hydroxybutyrate (GHB) or midazolam in combination with sufentanil was investigated in 45 patients undergoing coronary artery bypass grafting (CABG). Anaesthesia was induced with sufentanil, etomidate and pancuronium. After endotracheal intubation, anaesthesia was continued with sufentanil (2 μg kg−1 h−1) for all patients. Patients were randomized to receive supplementary propofol (2 mg kg−1 h−1, n=15), gamma-hydroxybutyrate (20 mg kg−1 h−1, n=15) or midazolam (0.06 mg kg−1 h−1, n=15). Haemodynamic measurements were performed after induction and at various times in the pre-bypass period. In the propofol group, a significant decrease in heart rate (HR 12%±3%), cardiac index (CI 23%±4%), mean arterial pressure (MAP 16%±3%) and left ventricular stroke work index (LVSWI 17%±4%) occurred until sternotomy was performed. With the exception of cardiac index, both midazolam and gamma-hydroxybutyrate produced similar haemodynamic effects: cardiac index was temporarily decreased (19%±4%) by midazolam and remained unchanged after gamma-hydroxybutyrate. In both groups, sternotomy was followed by temporary hypertension, associated with a significant rise in systemic vascular resistance. No electrocardiographical signs of ischaemia were observed in any patient. In the case of propofol and midazolam, gamma-hydroxybutyrate showed adequate haemodynamic stability especially after induction of anaesthesia and may also be a suitable agent for total intravenous anaesthesia in patients with coronary artery disease. However, during sternotomy, supplementary administration of opioids was required.

Hypertension and cardiovascular disease risk in women.

Hypertension and cardiovascular disease risk in women.

Endothelin blockade lowers total peripheral resistance in hemorrhagic shock recovery.

To determine whether endothelin (ET) has a role in maintaining circulatory support during hypotensive hemorrhage, we (1) examined cardiac and systemic hemodynamics after a 6-mL hemorrhage in the presence and absence of the ETA receptor blocker BQ-123, (2) examined cardiac and systemic hemodynamics during BQ-123 infusion in nonhemorrhaged rats, (3) measured changes in circulating immunoreactive endothelin (IR-ET) after a 6-mL hemorrhage, and (4) infused pathophysiological doses of ET-1 into rats anesthetized with thiobutabarbital. Twenty minutes after hemorrhage, cardiac output and mean arterial pressure had stabilized in part because of an increase in systemic vascular resistance from 0.86 +/- 0.04 (baseline) to 1.04 +/- 0.05 (20 minutes) mm Hg/mL per minute. The rise in systemic vascular resistance was temporally associated with a significant (24%) increase in circulating IR-ET from 29 +/- 2 to 36 +/- 3 pg/mL 20 minutes after hemorrhage. During BQ-123 infusion mean arterial pressure at 5, 10, and 20 minutes after hemorrhage was 9 +/- 2, 23 +/- 4, and 23 +/- 3 mm Hg lower than values obtained after hemorrhage alone (P < .05). Mean arterial pressure was unaffected by BQ-123 infusion at baseline and 30 minutes after hemorrhage. Systemic vascular resistance was not affected at baseline by BQ-123 infusion. However, systemic vascular resistance was significantly lower 5, 10, 20, and 30 minutes after hemorrhage during BQ-123 infusion compared with hemorrhage alone at each time point. Infusion of BQ-123 into nonhemorrhaged rats had no effect on mean arterial pressure, systemic vascular resistance, or cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

Haemodynamic and hormonal responses to losartan (DuP753/MK954) infusion during cardiac catheterization in conscious salt-deplete dogs.

1. Haemodynamic and hormonal responses to infused angiotensin II were studied in conscious salt-deplete dogs during infusion of D-glucose or losartan (DuP753/MK954). 2. Mean arterial pressure (118 +/- 13 mmHg) fell rapidly after losartan (60 min 106 +/- 18 mmHg) with a rise in heart rate (107 +/- 16 beats/min) from baseline (98 +/- 17 beats/min). Pressor responses to angiotensin II during D-glucose infusion (6 ng min-1 kg-1, 99 +/- 10 mmHg; 18 ng min-1 kg-1, 140 +/- 15 mmHg; 54 ng min-1 kg-1, 157 +/- 12 mmHg; 162 ng min-1 kg-1, 178 +/- 14 mmHg) showed a parallel shift during losartan infusion with very similar pressures in response to higher rates of angiotensin II infusion (54 ng min-1 kg-1, 108 +/- 17 mmHg; 162 ng min-1 kg-1, 138 +/- 14 mmHg; 486 ng min-1 kg-1, 155 +/- 14 mmHg; 1458 ng min-1 kg-1, 177 +/- 12 mmHg). Losartan caused a fall in baseline systemic vascular resistance. Despite the similar mean arterial pressure, the rise in systemic vascular resistance after angiotensin II during D-glucose infusion (162 ng min-1 kg-1, 8065 +/- 1967 dyn s cm-5) was reduced during losartan infusion (1458 ng min-1 kg-1, 6645 +/- 1720 dyn s cm-5. Losartan caused a small rise in cardiac output related to a rise in heart rate and increased stroke volume. Pressure infusions of angiotensin II caused a fall in cardiac output during D-glucose infusion, which was blocked during losartan infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acute carbohydrate administration on central and peripheral hemodynamic responses to mental stress.

Essential hypertension is closely related to conditions with impaired glucose tolerance and hyperinsulinemia. To evaluate a possible interaction between the sympathetic nervous system and carbohydrate ingestion on the circulatory responses to psychosocial stress, we compared the hemodynamic effects of an oral glucose challenge with those observed after placebo in 10 glucose-tolerant, normotensive young men at rest and during standardized mental stress. After glucose, resting cardiac output increased by 20% (p less than 0.05), which was mainly due to an increased heart rate (+14%; p less than 0.001). Since total peripheral resistance decreased by 13% (p less than 0.02), mean arterial pressure was unaffected by glucose. In spite of this, glucose loading was associated with a slight increase in systolic blood pressure and a gradual decrease of diastolic blood pressure. Resting forearm blood flow was unaffected by glucose. The stress response after placebo was characterized by the expected increase in cardiac output and mean arterial pressure, and an unchanged total peripheral resistance. By contrast, in the postprandial state the pressor response to stress was solely dependent on an increased systemic vascular resistance, and cardiac output was unaffected by stress. After glucose, the stress-induced muscular vasodilation in the forearm was reduced to 40% of that observed after placebo (p less than 0.01). Thus, acute carbohydrate administration has significant hemodynamic effects in humans. Furthermore, during the postprandial period there is a marked alteration of the pattern of the circulatory responses to psychosocial stress, characterized by attenuated muscular vasodilation and a rise in systemic vascular resistance.

Role of sulfidopeptide leukotrienes in synthetic smoke inhalation injury in sheep

Acute lung injury with smoke inhalation results in significant morbidity and mortality. Previously we have shown that synthetic smoke composed of carbon and acrolein, a common component of smoke, causes delayed-onset noncardiogenic pulmonary edema. To study the possible role of the vasoactive and edemagenic sulfidopeptide leukotrienes (SPLT) in smoke inhalation injury, we measured pulmonary hemodynamics, lung lymph flow, and SPLT and leukotriene (LT) B4 in lung lymph before and after 10 min of synthetic acrolein smoke exposure. After smoke exposure there was a significant rise in pulmonary vascular resistance caused by a rise in pulmonary arterial pressure, a fall in cardiac output, and no change in pulmonary capillary wedge pressure. This was accompanied by an increase in total systemic vascular resistance (P less than 0.05), lung lymph flow (P less than 0.05), and extravascular lung water-to-lung dry weight ratio (P less than 0.05). Both SPLT and LTB4 clearance rose significantly (P less than 0.05), but there was a 10-fold increase in SPLT over LTB4 clearance. In sheep pretreated with FPL55712, a SPLT antagonist, the early rise in pulmonary vascular resistance was attenuated, and the rise in systemic vascular resistance was blocked. This was associated with an attenuated and delayed fall in cardiac output. FPL55712 had no effect on lung lymph flow or extravascular lung water-to-dry weight ratio. SPLT, and especially LTD4, may have a role in increased pulmonary and systemic vascular resistance after smoke inhalation injury but does not appear to affect vascular permeability.

Reflex increase in blood pressure during the intracoronary administration of adenosine in man.

Infusion of adenosine (0.022-2.2 mg/min) into the left anterior descending (LAD) coronary artery of 26 patients produced a dose-dependent increase in blood pressure without a change in heart rate. At adenosine 2.2 mg/min, systolic pressure rose by 21.0 +/- 2.2 mmHg from 134 +/- 4.3 mmHg (P less than 0.001) and diastolic pressure increased by 10.4 +/- 1.1 mmHg from 76 +/- 1.9 mmHg (P less than 0.001). The rise in arterial pressure was associated with a 22 +/- 3.4% increase in systemic vascular resistance (P less than 0.01) and no change in cardiac output (-2.8 +/- 4.3%, P = NS). Plasma norepinephrine levels rose by 40 +/- 14% from 105 +/- 9 pg/ml (P less than 0.05) and epinephrine levels by 119 +/- 31% from 37 +/- 9 pg/ml (P less than 0.01). Right atrial infusion of adenosine produced insignificant hemodynamic effects, suggesting that systemic spillover of adenosine was not responsible for the observed effects. In 20 cardiac transplant patients with denervated hearts, LAD infusion of adenosine (2.2 mg/min) produced no change in systolic pressure (-0.1 +/- 1.6 mmHg from 139 +/- 3.4 mmHg, P = NS) and a decrement in diastolic pressure (-4.7 +/- 1.2 mmHg from 98 +/- 2.5 mmHg, P less than 0.01). Thus, infusion of adenosine into the LAD coronary artery causes a reflex increase in arterial pressure due to a rise in systemic vascular resistance, probably as a result of increased sympathetic discharge. This reflex pathway may be of importance in disease states such as myocardial ischemia, in which myocardial adenosine levels are elevated.

Complement-mediated hemodynamic depression in the early postburn period.

This study examines the influence of complement on systemic hemodynamics following severe thermal injury in rats. Animals were injected intraperitoneally at t = -36 and t = -24 hours with either cobra venom factor (20 units/kg/dose; n = 56) to delete circulating complement or with saline alone (n = 64). Rats within each subset were then subjected to either a 50% TBSA full-thickness scald burn or sham burn. Cardiac output (CO), mean arterial pressure (MAP), heart rate, systemic vascular resistance (SVR), stroke volume, and cardiac power as well as hematocrit and the change in per cent complement activity were determined at various time periods between 15 minutes and 25 hours after the burn. In normocomplementemic animals the burn produced a marked early (t = 3-6 hours) depression in CO and MAP with a rise in SVR. Over time the hemodynamics returned to normal (t = 12 hours) and eventually approached a hyperdynamic response (t = 24 hours). Serum hemolytic complement activity fell immediately and progressively after the burn, indicating significant complement activation. Complement depletion attenuated the early decline in CO and sharply lowered the rise in SVR in the early postburn period. In addition, complement depletion improved heart rate and stroke volume and appeared to preserve/enhance late (t = 24 hours) cardiac function. This study suggests that complement activation contributes to the depression in cardiac output in the early postburn period.